Phase 3
Completed N=403
A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Source: ClinicalTrials.gov NCT03525444 ↗Enrolled (actual)
403
Serious AEs
17.4%
Results posted
May 2020
Primary outcomePrimary: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) — -0.2; 13.6 percentage points — p=<0.0001
◆ Published Evidence
Highly cited
2,104citations · ~301 / year
Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele.
Summary
This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).
Linked Publications (2)
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Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele.
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Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) |
-0.4; 13.9 | <0.0001 sig |
| SECONDARY Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) |
-0.4; 13.9 | <0.0001 sig |
| SECONDARY Number of Pulmonary Exacerbations (PEx) |
113; 41 | <0.0001 sig |
| SECONDARY Absolute Change in Sweat Chloride (SwCl) |
-0.4; -42.2 | <0.0001 sig |
| SECONDARY Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score |
-1.9; 18.1 | <0.0001 sig |
| SECONDARY Absolute Change in Body Mass Index (BMI) |
0.09; 1.13 | <0.0001 sig |
| SECONDARY Absolute Change in Sweat Chloride |
0.1; -41.2 | <0.0001 sig |
| SECONDARY Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score |
-1.9; 18.1 | <0.0001 sig |
| SECONDARY Time-to-first Pulmonary Exacerbation (PEx) |
NA; NA | — |
| SECONDARY Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline |
0.04; 0.34 | — |
| SECONDARY Absolute Change in Body Weight |
0.5; 3.4 | — |
| SECONDARY Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
193; 188; 42; 28 | — |
| SECONDARY Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA |
5.02; 4.90; 4.99; 4.75; 2.16; 2.14 | — |
Eligibility Criteria
Key Inclusion Criteria
- Heterozygous for the F508del mutation (F/MF)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
Key Exclusion Criteria
- Clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- Solid organ or hematological transplantation
Other protocol defined Inclusion/Exclusion criteria may apply
Data sourced from ClinicalTrials.gov (NCT03525444) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.